Zeev Davidovitch -- Electric Braces

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**Zeev DAVIDOVITCH, *et al.***

**Electro-Orthodontics**

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***Science
News* 121 : 330 ( 15 May 1980 )**

**Shifting Teeth Faster Electrically**

Wearing braces to move and
straighten teeth can be a lengthy, painful experience. Now,
two University of Pennsylvania researchers believe electrical
stimulation of the gum may cut in half the time braces must be
worn. The researchers are just beginning a 3-year clinical
study with 60 female patients to test the mehtod.

Othrodontist Zeev Davidovitch, who
began the work in 1975 with materials scientist Edward
Korostoff, says orthodontists have conventionally used mechan
ical force to shift teeth. Mechanical devices that push or
pull a tooth apply force to a tooth's crown. The force is
transmitted downward to the root. there the bone tneds to
dissolve or resorb ahead of the moving tooth's root where the
pressure is high and to build up behind the root where the
pressure is low. the problem, says Davidovitch, is that tissue
remodeling doen'st happen overnight. "What we're doing with
electricity is simply enhancing the rate of tissue
remodeling", he says. Although braces are still necessary,
they are needed for a shorter time.

The electricity source is
approximately the size and shape of two nickels stuck
together. It consists of a transistor and several resisors and
batteries, encased in epoxy and dental acrylic plastic. The
device provides a constant current of between 15 and 20
microamperes at about 1.5 volts. Korostoff says the easily
installed movable circular unit attaches to the bracket
already installed for orthodontic wires and lies against the
gum, between the gum and the check. One major effort during
the first year of the clinical trials will be to reduce the
size of the device, Korostoff says. A graduate student
researcher, who has worn the device for a short time, says its
presence is noticeable, but it is not uncomfortable compared
with the normal discomfort people suffer when they wear
orthodontic braces. He says he did not feel the electric
current at all.

Although the method was tested
successfully on cats, Davidovitch admits that testing it on
humans is a new field. "We don't know what will happen", he
says. "There are many questions we haven't answered yet".
Initially, patients will weat the device for about 8 to 10
hours at night. "We may find that it's not sufficient", says
Davidovitch, "but this is why we plan to conduct these
experiments, to get the bugs out of the system".

Both Korostoff and Davidovitch are
optimistic that their method will work on humans as well as it
did on cats, and they are very excited about their work.
Through the university of Pennsylvania, they hold a patent on
the method and device now being tested at the university's
School of Dental Medicine.

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***Moneysworth*, mid-1980s**

**Effect of Electric Braces Shocking**

*Philadelphia* -- Electric
braces, which could take a big bite out of the amount of time
usually needed to straighten teeth, have been developed by
researchers at the University of Pennsylvania School of Dental
Medicine.

Dr Zeev Davidovitch, orthodontics
professor and dead of the research team, says miniature
batteries, transistors and resistors produce and regulate the
low-level electric current in the device.

The electrical-mechanical device,
used with conventional orthodontics braces, has been
successfully tested on animals. Davidovitch says it could
straighten teeth twice as fast as regular breaces and be no
more inconvenient. He hopes to begin a 3-year study on humans
soon. "The bulkiness of this power pack resembles the
bulkiness of an extension screw, [often] used to expand
palates", he says.

"It can be easily taken in and out
and should pose no dicomfort to the patient. he can weat it
only at night, and he can't throw it out of adjustment unless
he steps on it or breaks it with a hammer."

In initial tests, sandard braces
were placed on one side of a cat's mouth, the device on teh
other. An electrode was placed on either side of a tooth and a
small amount of electricity was generated.

Weeks later, the researchers sound
that where there was electrical stimulation tooth movement was
twice as fast. The scientists also found that because cell
stimulation occurs a few minutes after electricity is
intriduced, the device does not have to be worn 24 hours a
day.

"When you try to move teeth, you
apply forces -- the wires, srings and elastic bands -- to the
teeth. The force is transmitted to the surrounding tissue,"
Davidovitch explains.

"We thought if we could get more
cells involved in the surrounding tissue, we would get rapid
tooth movement."

It has been estimated that only 5
to 10 percent of those who need orthodontia receive it,
Davidovitch says. If treatment time, which often runs into
years, can be halved, more patients will be willing to undergo
treatment, he predicts.

---

  
**US4153060**   

**Method and Apparatus for
Electrically Enhanced Bone Growth and Tooth Movement**

**1979-05-08**   
**KOROSTOFF EDWARD; DAVIDOVITCH ZEEV**   
Classification:    - international: 
A61C7/00; A61N1/05; A61N1/32; A61C7/00; A61N1/05; A61N1/32;
(IPC1-7): A61N1/36   
**Abstract --** Disclosed is a method and apparatus for
electrically stimulating bone growth and tooth movement in the
mouths of mammals. A positive electrode is placed on the gum
surface adjacent the bone structure which is to be resorbed. A
negative electrode is placed on the gum surface adjacent the
bone tissue which is to be accreted or built up. A current
source is connected, such that a small current flows between
the electrodes, which has the effect of stimulating bone
growth in a specific direction. In a preferred embodiment, the
electrodes are placed on the gum surface adjacent a tooth, the
positive electrode on the side towards which the tooth should
move, and the negative on the side from which the tooth will
move. Application of a small current to the electrodes will
enhance the repositioning of the tooth in conjuction with
normal orthodontic practices.

**BACKGROUND OF THE INVENTION**

The present invention relates to
orthodontic techniques in general, and the reduction in time
required for specific tooth movement in particular.

Orthodontic tooth movement
presently is accomplished by the application of mechanical
forces to teeth. An apparatus is connected inside the mouth of
a patient which applies, through the use of springs, rubber
bands, or other means, a mechanical force in the direction of
desired tooth movement. These forces cause the bone to resorb
(be moved) in the direction of force and cause the bone to
grow on the other side of the tooth.

This process of orthodontic force
application enables teeth to move in the mouth within the
boundaries of the neighboring tissues. The tooth movement is
clarified by Wolff's Law which states, in effect, that bone
under mechanical stress is remodeled to accomodate or reduce
the stress. The unfortunate practical aspect to known
techniques of orthodontic movement is that the mechanical
apparatus, or "braces", must be worn by the patient for
extended periods of time, often several years or more.

U.S. Pat. No. 3,842,841 teaches the
application of a direct current to aid healing of bone
fractures in the human body, but requires surgical
implantation. A negative electrode (cathode) is surgically
inserted into the site of a fracture, and a positive electrode
(anode) is taped to the skin elsewhere. Although the precise
biological process is not understood, the current flowing
through the factured bone increases the healing rate of the
damaged bone tissue.

However, to date, there have been
no substantial improvements in enhancing tooth movement to
reduce the total amount of time over which an orthodontic
appliance must be used in order to accomplish a given amount
of tooth movement or repositioning.

**SUMMARY OF THE INVENTION**

Therefore, in view of the
foregoing, it is an object of the present invention to
reposition teeth in a patient's mouth by applying an
electrical potential to the patient's gums in the immediate
vicinity.

It is a further object of the
present invention to increase the rate of movement of teeth
undergoing mechanical stress in accordance with known
orthodontic practices.

It is a still further object of the
present invention to provide an electronic circuit capable of
being retained in conjunction with an existing orthodontic
appliance for providing a constant current output to
electrodes located adjacent to a tooth to be repositioned.

It is an additional object of the
present invention to provide a method and apparatus for
stimulating and controlling bone growth in a patient's mouth
in order to correct alveolar bone defects, close cleft
palates, or maintain the alveolar ridge in edentulous patients
(those who have lost their teeth).

In accordance with the above, the
other objects, a method and apparatus for the initiation and
enhancement of tooth movement comprises the disposition of an
anodic electrode in the direction of applied force and a
cathodic electronic on the opposite side of the tooth to be
moved. A current source is connected to the two electrodes
which causes the tooth to be repositioned either solely or in
combination with an existing orthodontic appliance.

The application of a small current,
through appropriate surface electrodes in the mouth, also can
be utilized to stimulate bone accretion in the vicinity of a
cathodic electrode and bone resorption in the vicinity of an
anodic electrode.

**BRIEF DESCRIPTION OF THE
DRAWINGS**

A more complete appreciation of the
invention and the attendant advantages thereof will be more
clearly understood by reference to the following drawings
wherein:

**FIG. 1** is a bottom view of
an orthodontic appliance showing the location of the apparatus
in relation to the orthodontic springs;

![](fig1.jpg)

**FIG. 2** is a side view
showing the placement of the electrodes according to a
preferred embodiment;

![](fig23.jpg)

**FIG. 3** is a bottom view
showing a preferred embodiment of the anode and cathode
electrodes;

**FIG. 4** is an electrical
schematic of a preferred embodiment of a constant current
circuit;

![](fig4.jpg)

**FIG. 5** is a perspective view
showing the placement of the cathode electrode to correct
aveolar bone defects;

![](fig5.jpg)

**FIG. 6** is a bottom view of
the placement of cathode electrodes for the correction of a
cleft palate; and

![](fig6.jpg)

**FIG. 7** is a perspective view
showing the placement of the cathode electrode in an
edentulous patient.

![](fig7.jpg)

**DETAILED DESCRIPTION OF A
PREFERRED EMBODIMENT**

Referring now to the drawings
wherein like reference characters designate like parts
throughout the several views, FIG. 1 is a bottom view of an
orthodontic appliance along with the present invention fitted
to a cat's mouth in accordance with known techniques. Although
the present application was reduced to practice and
demonstrated on a cat tooth, the anatomy and histology of the
cat canine and its surrounding tissues is similar to
one-rooted human teeth. Although the present description will
be of the application of the present invention to the test
animals, the invention is clearly of use in the human
application, which would provide no unobvious difficulties. A
base plate 10 is located in the roof of the patient's mouth
and fixed to the premolar teeth 12 by conventional clamps 14.
Orthodontic springs 16 are connected to the rearmost premolar
teeth 12 and the teeth to be repositioned, in this instance,
canine teeth 18 and 20.

An anode electrode 22 and a cathode
electrode 24 are placed such that they are in contact with the
gingival tissue 26. The anode 22 is placed adjacent the tooth
in the direction of desired movement, in this instance,
towards spring 16. The cathode 24 is placed on the opposite
side of tooth 18. The anode 22 and cathode 24 are connected to
positive and negative leads from power pack 28 contained in
base plate 10.

The details of the power pack's
internal features can be seen by reference to FIG. 4. The
negative terminal 29 is connected to the negative side of
battery 30, with the positive side of the battery 30 connected
to transistor 32. Transistor 32 is interconnected with
transistor 34 and resistor 36 and, then, to the positive
terminal 38. In this preferred embodiment, a constant current
of approximately 20 microamperes is provided over a range of
tissue impedances, such that the changing impedance between
the anode and cathode does not substantially affect the amount
of current flowing therebetween.

FIGS. 2 and 3 are side and bottom
views, respectively, of a preferred electrode placement, with
the direction of desired movement shown by arrow 40. Although
the mechanical force generating system comprising orthodontic
springs 16, shown in FIG. 1, are not included in FIGS. 2 and
3, they could clearly be added to further enhance the movement
of tooth 18 in direction 40. However, tooth movement can be
accomplished solely by means of the electrical stimulation
shown in FIGS. 2 and 3, and this remains one embodiment.

However, the preferred embodiment
of the present invention is the use of the electrodes to
increase the rate of movement of teeth undergoing orthodontic
treatment.

In a test of the FIG. 1 apparatus,
five female cats (Group A) had both canine teeth tipped in the
direction of arrow 40 by coil springs generating 80 grams of
force for a period of 14 days. Five additional female cats
(Group B) had both canines tipped in the same direction.
However, Group B cats also had a stainless steel cathode 24
and a gold anode 22 connected to the electrical circuit of
FIG. 4, with the electrode placement shown in FIG. 1. Both
electrodes were in contact with the gingival tissues at, and
partially surrounding, the area of the alveolar bone crest.
Dummy electrodes (not shown) were also placed in contact with
the gingival tissues surrounding canine tooth 20, but were not
connected to power pack 28.

In the Group A animals, the rate of
canine tooth movement was similar on both sides. In Group B,
however, the rate was unequal with the activated electrode
side doving canine tooth 18 twice as much as electrically
unactivated canine tooth 20. For instance, the distance
between incisors 42 and unactivated canine tooth 20 increased
by 0.29 mm after seven days, and an additional 0.17 mm after
fourteen days. The distance between the incisors 42 and the
electrically activated canine 18 after seven days had
increased 0.58 mm, and after fourteen days an additional 0.61
mm. Because both canine teeth 18 and 20 had identical
mechanical forces applied thereto (by springs 16), the
increased rate of movement of canine tooth 18 is attributable
to the application of electric current to the surrounding gum
tissues.

Because the present invention
essentially doubles the rate of movement, the length of time
necessary to achieve a repositioning of a tooth would be cut
in half. Although human tests have not yet been conducted, it
is believed the results will be similar to those shown in the
cat studies, because of the similarity of cat canine teeth and
their surrounding tissues to single root human teeth. Thus,
the applicability to the human orthodontic patient is believed
obvious in view of the above teachings. The application to the
human patient may require current levels different from the 21
microamps applied in the cat embodiment.

Similarly, different combinations
of implanted and surface electrodes will be obvious to those
of ordinary skill in the art in view of the applicants'
teachings. Although, a constant current supply source was
utilized in a preferred embodiment, constant voltage with a
variable current source may be used with slightly different
results. Additionally, an alternating current with a D.C.
impressed thereon would also work. The only requirement being
that one electrode be substantially anodic and the other
substantially cathodic, i.e., the total current (AC and DC
combined) is more in one direction than the other.

The current supply means utilized
in the cat tests delivered a constant current of 21.+-. 4 .mu.
amps. It is believed that some variation may be necessary for
individual patients, but that current ranges of between 5 and
100 microamps will be useful in obtaining similar results in
humans. Additionally, where, as will be seen, extended
electrodes are utilized, as in FIGS. 6 and 7, the total
current applied to the extended electrode (or a series of
button electrodes) must be increased in order to maintain a
current density at the gum tissue, sufficient to cause bone
accretion or resorption.

The present embodiments indicate
the placement of electrodes on the soft gingival tissue
adjacent, but not in contact with, the bone in order to
produce the desired effect, although there is no indication
that placement of the electrodes on the bone itself would have
a deleterious effect. A preferred circuit for a constant
current power supply is shown in FIG. 4, although many compact
intra-oral power supplies will become apparent to those
skilled in the art in view of the applicants' invention.

The application of surface
electrodes to stimulate controlled bone growth can also supply
the solution for non-surgical correction of alveolar bone
defects, and cleft palates. FIG. 5 depicts a tooth 50, gum 52,
with the alveolar bone ridge 54. A defect in the alveolar bone
ridge is indicated at 56. The placement of a cathodic surface
electrode 24 on the gum in the region of the defect 56 could
stimulate bone growth so as to eliminate the defect. The
anodic surface electrode (not shown) would be located
elsewhere in the patient's mouth.

A similar application of the
surface electrode could be utilized in conjunction with a
cleft palate, as shown in FIG. 6. The region of the cleft 60
would be gradually filled by bone due to the electrical
stimulation of cathodic electrodes 24 placed on the surface of
tissues covering the bony palate 62. As in FIG. 5, the anodic
electrode would be located elsewhere in the patient's mouth.
As in all depictions of the use of surface electrodes, only in
the region where bone growth is to be stimulated, or the bone
is to be resorbed, is the electrode in contact with the gum,
or gingival tissues. Elsewhere, the wires connecting the
surface electrodes to the power supply would be insulated so
as to restrict bone accretion, or resorption, to the desired
area. It has been proposed that over an extended period of
time, the bone accretion to the bony palate in the vicinity of
electrodes 24 would result in a buildup, and eventual closure,
of the cleft region 60 in the victim of a cleft palate.

It has been found that the bone has
piezoelectric properties: that is to say, when a force is
applied to the tooth, the resulting force on the bone
generates very small, but measurable, electrical currents. It
is believed that the application of these minute currents
stimulate, and maintain, the alveolar bone ridge, which serve
as the base for anchoring of human teeth. However, edentulous
patients suffer from a gradual resorption of the alveolar bone
ridge in the mouth, which makes it more and more difficult to
anchor false teeth in the patient's mouth. It is believed that
the absence of real teeth in the edentulous patient causes the
termination of the minor stimulation currents necessary for
the maintenance of the alveolar bone ridge and, consequently,
the ridge resorbs into the roof of the mouth.

FIG. 7 depicts an arrangement of
cathodic electrode 24, wherein it would be placed adjacent the
alveolar bone ridge in a patient's mouth. The application of a
suitable current supply with the anode (not shown) located
elsewhere in the mouth may provide sufficient stimulation to
the alveolar bone ridge, such that it is maintained, or even
reformed, in the edentulous patient. Obviously, the power
supply, and appropriate electrodes, could be located in the
bridge work of false teeth, and would be applicable both to
the upper and lower bond ridges.

Although the invention has been
described relative to a specific embodiment thereof, it is not
so limited and many modifications and variations thereof will
be readily apparent to those skilled in the art in light of
the above teachings. It is, therefore, to be understood that,
within the scope of the appended claims, the invention may be
practiced otherwise than as specifically described.

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**Biocompatible electrode and use in
orthodontic electroosteogenesis**   

**US Patent # 4854865**

**Abstract**: An improved method
of orthondontic electroosteogenesis comprises providing a
biocompatible anode having a noble metal portion in engagement
with an electrolytic gel portion comprising agarose and an
electrolyte, where the anode gel portion is in engagement with
epithelial gingiva at an area of osteoclastic or osteoblastic
activity, and a biocompatible cathode having a noble metal
portion in engagement with an electrolytic gel portion
comprising agarose, an electrolyte, and a weak, biocompatible
acid, where the cathode gel portion is in engagement with
epithelial gingiva at an area of osteoblastic or osteoclastic
activity. Electric current is then applied across the anode
and cathode to stimulate osteogenesis. The invention also
comprises biocompatible electrodes for electric stimulation of
tissue.   
 

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[**http://cro.sagepub.com/cgi/content/abstract/2/4/411**](http://cro.sagepub.com/cgi/content/abstract/2/4/411)

***Critical Reviews in Oral
Biology & Medicine*, Vol. 2, No. 4, 411-450 (1991)**
  
DOI: 10.1177/10454411910020040101

**Tooth Movement**

**Zeev Davidovitch**

*Department of Orthodontics, The
Ohio State University College of Dentistry, Columbus, Ohio*

This article reviews the evolution
of concepts regarding the biological foundation of
force-induced tooth movement. Nineteenth century hypotheses
proposed two mechanisms: application of pressure and tension
to the periodontal ligament (PDL), and bending of the alveolar
bone. Histologic investigations in the early and middle years
of the 20th century revealed that both phenomena actually
occur concomitantly, and that cells, as well as extracellular
components of the PDL and alveolar bone, participate in the
response to applied mechanical forces, which ultimately
results in remodeling activities.

Experiments with isolated cells in
culture demonstrated that shape distortion might lead to
cellular activation, either by opening plasma membrane ion
channels, or by crystallizing cytoskeletal filaments.
Mechanical distortion of collagenous matrices, mineralized or
non-mineralized, may, on the other hand, evoke the development
of bioelectric phenomena (stress-generated potentials and
streaming potentials) that are capable of stimulating cells by
altering the electric charge on their membrane or their fluid
envelope. In intact animals, mechanical perturbations on the
order of about 1 min/d are apparently sufficient to cause
profound osteogenic responses, perhaps due to matrix
proteoglycan-related "strain memory".

Enzymatically isolated human PDL
cells respond biochemically to mechanical and chemical
signals. The latter include endocrines, autocrines, and
paracrines. Histochemical and immunohistochemical studies
showed that during the early places of tooth movement, PDL
fluids are shifted, and cells and matrix are distorted.
Vasoactive neurotransmitters are released from periodontal
nerve terminals, causing leukocytes to migrate out of adjacent
capillaries. Cytokines and growth factors are secreted by
these cells, stimulating PDL cells and alveolar bone lining
cells to remodel their related matrices. This remodeling
activity facilitates movement of teeth into areas in which
bone had been resorbed.

This emerging information suggests
that in the living mammal, many cell types are involved in the
biological response to applied mechanical stress to teeth, and
thereby to bone. Essentially, cells of the nervous, immune,
and endocrine systems become involved in the activation and
response of PDL and alveolar bone cells to applied stresses.
This fact implies that research in the area of the biological
response to force application to teeth should be sufficiently
broad to include explorations of possible associations between
physical, cellular, and molecular phenomena. The goals of this
investigative field should continue to expound on fundamental
principles, particularly on extrapolating new findings to the
clinical environment, where millions of patients are subjected
annually to applications of mechanical forces to their teeth
for long periods of time in an effort to improve their
position in the oral cavity. Recently developed research tools
such as cell culture techniques and immunologic probes, are
the best hope for enhancing this development.

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**USP 4570637**   
**Electrode**

Robert L. Gomes // Joseph P.
Maffione

**Abstract --** An improved
medical electrode is particularly adapted for transmitting DC
currents. The electrode includes (1) an electrically
conductive substrate electrically connected to a stud member
and chemically inert with respect to the electrically and
ionically conductive material, such as a gel, coupling the
electrode to the skin of the user, and (2) a predetermined
amount of an electrically-conductive material, preferably
silver, disposed on the substrate in spaced relationship to
the stud member and interfacing with the electrically and
ionically conductive material.

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**USP 4757804**   
**Device for Electromagnetic Treatment of
Living Tissue**

July 19, 1988   
Griffith, et al.

Other References:  "Fracture
Healing in the Rabbit Fibula When Subjected to Various
Capacitively Coupled Electrical Fields" by Brighton et al,
Journal ofOrthopedic Research, vol. 3, No. 3, 1985..   
"Electrical Stimulation of Hard and Soft Tissues in Animal
Models" by Jonathan Black, Ph.D., Clinics in Plastic Surgery,
vol. 12, No. 2, Apr. 1985..   
"Bioelectric Stimulation of Bone Formation: Methods, Models,
and Mechanisms" by Spadaro, Journal of Bioelectricity, vol. 1,
No. 1, 1982..   
"A Review of Electromagnetically Enhanced Soft Tissue Healing"
by Cyril B. Frank, M.D. and Andrew Y. J. Szeto, Ph.D..   
"Treatment of Osteonecrosis of the Hip with Specific, Pulsed
Electromagnetic Fields (PEMFs): A Preliminary Clinical Report"
by C. A. L. Bassett et al, Journal of Bone Circulation..

**Abstract:**  A solenoid
device for treatment of body tissue such as bones or other
regions with pulsed signals comprises a flexible flat belt for
encircling a body part or cast surrounding a body part
containing tissue to be treated. The belt has a plurality of
parallel conductors extending along its length and has its
opposite ends offset by one or more conductor spacings. The
resultant aligned conductor ends are connected together to
form at least one continuous coil, with the resultant
unconnected outer conductor ends at opposite sides of the belt
comprising inputs across which a suitable electrical signal
can be connected. An adjustment device or buckle is mounted on
the belt to allow the diameter of the belt to be adjusted. The
buckle traps a doubled over portion of the belt circumference
which is adjustable in length to change the diameter of the
device to closely fit the underlying body part or cast.

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**Relaxins**

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**US Patent 6984128**   
**Methods for Enabling and Stabilizing
Tooth Movement**

**BACKGROUND OF THE INVENTION**

**1. Field of the Invention**

The present invention relates
generally to medical apparatus and methods. More particularly,
the present invention relates to methods and systems for
facilitating, accelerating, and stabilizing tooth movement
before, during and after orthodontic procedures.

Orthodontic procedures suffer from
four major problems. First, the braces or other appliances
which effect the tooth movement must be worn for long periods
of time. Second, even after a successful orthodontic
treatment, the teeth often relapse towards their original
positions once the braces or other treatment appliances are
removed. Third, the mechanically induced movement of teeth can
cause significant discomfort to the patient. Fourth, the
wearing of braces is esthetically displeasing, uncomfortable,
and compromises oral hygiene. While recently introduced clear
plastic visible "aligners" largely overcome the latter
problems, such aligners are not suitable for all patients.
Moreover, the aligners do not reduce treatment time, do not
reduce the risk of relapse, and do not lessen the pain
associated with tooth movement in the jaw.

For these reasons, it would be
desirable to provide improved orthodontic technologies for
moving teeth which overcome at least some of the problems
noted above. In particular, it would be desirable to provide
orthodontic methods and systems which can reduce the time
necessary to effect a desired tooth movement, which can reduce
the pain associated with tooth movement, which can reduce the
tendency of teeth to relapse to their original positions after
the orthodontic treatment is stopped, and/or which can reduce
the time in which unsightly braces need to be worn.

**2. Description of Background Art**

Nicozisis et al. (2000) Clin.
Orthod. Res. 3:192-201, describes experiments which
demonstrate the presence of endogenous relaxin in cranial
tissue of mice and speculates that relaxin may be used as an
adjunct to orthodontic or surgical therapy to promote
manipulation of sutural tissues or affect stability. The
application of electrical current to stimulate bone growth and
remodeling in orthodontic procedures is described in U.S. Pat.
Nos. 4,854,865; 4,519,779; and 4,153,060. Appliances for local
and systematic drug delivery to the gingival tissues are
described in U.S. Pat. Nos. 6,159,498, 5,633,000; 5,616,315;
5,575,655; 5,447,725; 5,294,004; 4,959,220; 4,933,183;
4,892,736; 4,685,883; and Re. 34,656. Polymeric shell
appliances for repositioning teeth are described in U.S. Pat.
No. 5,975,893. The full disclosures of each of the above U.S.
patents are incorporated herein by reference.

**BRIEF SUMMARY OF THE INVENTION**

The present invention provides
improved methods and systems for repositioning teeth in
patients. In addition, the present invention provides improved
methods and systems for stabilizing teeth which have already
been repositioned in order to reduce or eliminate the tendency
of the repositioned teeth to relapse, i.e., move back toward
their prior positions. The methods for repositioning teeth
comprise applying force to at least one tooth, and typically
to more than one tooth and/or to different teeth over time, in
the jaw of the patient. For both repositioning or stabilizing,
tissue remodeling and/or an angiogenic substance(s) is
administered to the patient to promote remodeling of
periodontal tissue surrounding the root(s) of the tooth or
teeth to be moved. Preferred substance(s) will bind to and
activate the relaxin receptor in the tissues which anchor the
teeth or other craniofacial structures. Most preferred is
relaxin or an analog or mimetic thereof which combines tissue
remodeling activity with angiogenic activity. Analogs include
peptides, oligomers, fragments, etc. which comprise the active
region of native relaxin and mimetics include small molecule
drugs, typically below 2 kD, designed to mimic the activity of
native relaxin. Alternatively, substance(s) with predominantly
angiogenic activity could be selected, such as VEGF, bFGF,
estrogen, nitrous oxide, naltrexone, or the like. Further
alternatively, collagenases or other tissue-softening enzymes
could be utilized to promote periodontal tissue remodeling
according to the present invention. In some instances, it may
be desirable to combine two or more tissue remodeling and/or
angiogenic substance(s) having differing activities. In other
instances it may be desirable to deliver different tissue
remodeling and/or angiogenic substance(s) at different times
during the orthodontic treatment and/or to different regions
of the periodontal tissue.

The term "relaxin" means human
relaxin, including intact full length relaxin or a portion of
the relaxin molecule that retains biological activity [as
described in U.S. Pat. No. 5,023,321, preferably recombinant
human relaxin (H2)] and other active agents with relaxin-like
activity, such as Relaxin and portions that retain biological
activity Like Factor (as described in U.S. Pat. No. 5,911,997
at SEQ ID NOS: 3 and 4, and column 5, line 27-column 6, line
4), relaxin analogs and portions that retain biological
activity (as described in U.S. Pat. No. 5,811,395 at SEQ ID
NOS: 1 and 2, and column 3, lines 16-40), and agents that
competitively displace bound relaxin from a receptor. Relaxin
can be made by any method known to those skilled in the art,
for example, as described in any of U.S. Pat. Nos. 5,759,807;
4,835,251 and co-pending U.S. Ser. No. 07/908,766 (PCT
US90/02085) and Ser. No. 08/080,354 (PCT US94/0699).

The tissue remodeling and/or
angiogenic substance(s) will be delivered at a delivery rate
and a total dosage which are selected to facilitate tooth
repositioning and tissue remodeling. Typically, the dosage
rates will be in the range from 1 ng to 500 ?g per day,
usually from 10 ng/day to 20 ?g/day, preferably from 20 ng/day
to 10 ?g/day. The dosage and other aspects of the delivery may
be adjusted from time-to-time in response to the effectiveness
of treatment, such as the resistance of a particular tooth or
group of teeth, where the dosage might be increased if
resistance is not sufficiently reduced in response to an
initial dosage.

&c...

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**WO/2004/041106**   
**METHODS AND SYSTEMS FOR ENABLING AND
STABILIZING TOOTH MOVEMENT**

**BACKGROUND OF THE INVENTION**

[0001] 1. Field of the Invention.
The present invention relates generally to medical apparatus
and methods. More particularly, the present invention relates
to methods and systems for facilitating, accelerating, and
stabilizing tooth movement before, during and after
orthodontic procedures.

[0002] Orthodontic procedures
suffer from four major problems. First, the braces or other
appliances which effect the tooth movement must be worn for
long periods of time. Second, even after a successful
orthodontic treatment, the teeth often relapse towards their
original positions once the braces or other treatment
appliances are removed. Third, the mechanically induced
movement of teeth can cause significant discomfort to the
patient. Fourth, the wearing of braces is esthetically
displeasing, uncomfortable, and compromises oral hygiene.

While recently introduced clear
plastic visible"aligners"largely overcome the latter problems,
such aligners are not suitable for all patients. Moreover, the
aligners do not reduce treatment time, do not reduce the risk
of relapse, and do not lessen the pain associated with tooth
movement in the jaw.

[0003] For these reasons, it would
be desirable to provide improved orthodontic technologies for
moving teeth which overcome at least some of the problems
noted above. In particular, it would be desirable to provide
orthodontic methods and systems which can reduce the time
necessary to effect a desired tooth movement, which can reduce
the pain associated with tooth movement, which can reduce the
tendency of teeth to relapse to their original positions after
the orthodontic treatment is stopped, and/or which can reduce
the time in which unsightly braces need to be worn.

**[0004] 2. Description of
Background Art.**

Nicozisis et al. (2000) Clin.
Orthod. Res. 3: 192-201, describes experiments which
demonstrate the presence of endogenous relaxin in cranial
tissue of mice and speculates that relaxin may be used as an
adjunct to orthodontic or surgical therapy to promote
manipulation of sutural tissues or affect stability. The
application of electrical current to stimulate bone growth and
remodeling in orthodontic procedures is described in U. S.
Patent Nos. 4,854, 865; 4,519, 779; and 4,153, 060. Appliances
for local and systematic drug delivery to the gingival tissues
are described in U. S. Patent Nos. 6,159, 498, 5,633, 000;
5,616, 315; 5,575, 655; 5,447, 725; 5,294, 004; 4,959, 220;
4,933, 183; 4,892, 736; 4,685, 883; and Re. 34,656. Polymeric
shell appliances for repositioning teeth are described in U.
S. Patent No. 5,975, 893. The full disclosures of each of the
above U. S. Patents are incorporated herein by reference.

**BRIEF SUMMARY OF THE INVENTION** [0005]

The present invention provides
improved methods and systems for repositioning teeth in
patients. In addition, the present invention provides improved
methods and systems for stabilizing teeth which have already
been repositioned in order to reduce or eliminate the tendency
of the repositioned teeth to relapse, i. e. , move back toward
their prior positions.

The methods for repositioning teeth
comprise applying force to at least one tooth, and typically
to more than one tooth and/or to different teeth over time, in
the jaw of the patient.

For both repositioning or
stabilizing, tissue remodeling and/or an angiogenic substance
(s) is administered to the patient to promote remodeling of
periodontal tissue surrounding the root (s) of the tooth or
teeth to be moved. Preferred substance (s) will bind to and
activate the relaxin receptor in the tissues which anchor the
teeth or other craniofacial structures. Most preferred is
relaxin or an analog or mimetic thereof which combines tissue
remodeling activity with angiogenic activity. Analogs include
peptides, oligomers, fragments, etc. which comprise the active
region of native relaxin and mimetics include small molecule
drugs, typically below 2 kD, designed to mimic the activity of
native relaxin. Alternatively, substance (s) with
predominantly angiogenic activity could be selected, such as
VEGF, bFGF, estrogen, nitrous oxide, naltrexone, or the like.
Further alternatively, collagenases or other tissue-softening
enzymes could be utilized to promote periodontal tissue
remodeling according to the present invention. In some
instances, it may be desirable to combine two or more tissue
remodeling and/or angiogenic substance (s) having differing
activities. In other instances it may be desirable to deliver
different tissue remodeling and/or angiogenic substance (s) at
different times during the orthodontic treatment and/or to
different regions of the periodontal tissue.

[0006] The term"relaxin"means human
relaxin, including intact full length relaxin or a portion of
the relaxin molecule that retains biological activity [as
described in U. S. Pat.

No. 5,023, 321, preferably
recombinant human relaxin (H2) ] and other active agents with
relaxin-like activity, such as Relaxin and portions that
retain biological activity Like Factor (as described in U. S.
Pat. No. 5, 911, 997 at SEQ ID NOS: 3 and 4, and column 5,
line 27- column 6, line 4), relaxin analogs and portions that
retain biological activity (as described in U. S. Pat. No.
5,811, 395 at SEQ ID NOS: 1 and 2, and column 3, lines 16-40),
and agents that competitively displace bound relaxin from a
receptor. Relaxin can be made by any method known to those
skilled in the art, for example, as described in any of U. S.
Pat. Nos. 5,759, 807; 4,835, 251 and co-pending U. S. Ser.
Nos. 07/908, 766 (PCT US90/02085) and 08/080, 354 (PCT
US94/0699).

[0007] The tissue remodeling and/or
angiogenic substance (s) will be delivered at a delivery rate
and a total dosage which are selected to facilitate tooth
repositioning and tissue remodeling. Typically, the dosage
rates will be in the range from 1 ng to 500 ug per day,
usually from 10 ng/day to 20 ug/day, preferably from 20 ng/day
to 10 ug/day. The dosage and other aspects of the delivery may
be adjusted from time-to-time in response to the effectiveness
of treatment, such as the resistance of a particular tooth or
group of teeth, where the dosage might be increased if
resistance is not sufficiently reduced in response to an
initial dosage.

&c...

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